Prompt and permanent closure of excised full-thickness burns remains a critical factor in a patient's recovery from massive burn injuries. Hypothetically, Integra Artificial Skin (Integra) may replace the need for allografts for immediate wound coverage, and cultured skin substitutes (CSS) that contain stratified epithelium may replace the need for autografts for definitive wound closure. To test this hypothesis, 3 patients with full-thickness burns of greater than 60% of their total body surface areas had their eschar excised within 14 days of admission. Integra was applied, and a skin biopsy was collected from each patient for the preparation of CSS. At 3 weeks or more after the application of the Integra and the collection of skin biopsies, the outer silastic cover of the Integra was removed and CSS were grafted. The CSS were irrigated with nutrients and antimicrobials for 6 days and then dressed with antimicrobial ointment and cotton gauze. Treated wounds were traced on days 14 and 28 after the grafting of CSS for determination of engraftment and wound closure, respectively. Cost analysis was not performed. Engraftment on postoperative day (POD) 14 was 98%+/-1% (mean +/- standard error of the mean), the ratio of closed:donor areas on POD 28 was 52.3+/-5.2, and no treated sites required regrafting. The histology of the closed wounds showed stable epithelium that covered a layer of newly formed fibrovascular tissue above the reticulated structure of the degrading Integra. The clinical outcomes of the closed wounds after POD 28 demonstrated smooth, pliable, and hypopigmented skin. Two patients who had received CSS grafts over Integra on their backs were positioned supine on air beds from POD 8 or POD 9 with minimal graft loss because of mechanical loading. One patient with a full-thickness burn of 88% of the total body surface area was covered definitively at 55 days postburn. These results demonstrate that the combination of CSS and Integra can accomplish functionally stable and cosmetically acceptable wound closure in patients with extensive full-thickness burns. This combination of alternatives to the conventional grafting of split-thickness skin permits the substitution of cadaveric allograft with Integra and the substitution of donor autograft with CSS. This approach to the closure of excised full-thickness burns is expected to reduce greatly the time to definitive closure of burn wounds and to reduce the morbidity associated with the harvesting of donor sites for split-thickness skin autografts.